QbD-based co-loading of paclitaxel and imatinib mesylate by protamine-coated PLGA nanoparticles effective on breast cancer cells

Abstract

Aim: Paclitaxel and imatinib mesylate are drugs used in the treatment of breast cancer. Conventional drug-delivery systems have limitations in the effective treatment of breast cancer using the drugs. Materials & methods: Combination index studies were used to identify the optimum ratio of both drugs showing maximum synergistic effect. Using a systematic quality-by-design approach, protamine-coated PLGA nanoparticles co-loaded with paclitaxel and imatinib mesylate were formulated. Further characterization and cell line evaluations were performed. Results: Encapsulation efficiency obtained was 92.54% for paclitaxel and 75.12% for imatinib mesylate. A sustained (24 h) and controlled zero-order drug release was obtained. Conclusion: Formulated nanoparticles had a low IC₅₀ value and enhanced cellular uptake.

GRAPHICAL ABSTRACT

Article highlights

• Paclitaxel and imatinib (PXL and IMA) show synergistic efficacy against the MCF-7 cell line of breast cancer.

• PXL and IMA in the ratio of 4:1 show maximum effect and lowest combination index (CI).

• Quality-by-design methodology led to optimization and systematic formulation of coloaded protamine-coated PLGA nanoparticles.

• Protamine decreased the initial burst release of the formulations.

• A sustained zero-order drug release was obtained for both the formulations.

• Protamine coating was clearly visible on images using transmission electron microscopy analysis.

• Significant reduction in IC₅₀ values showing increased cytotoxicity was observed.

• Roughly 30-fold increase in cellular uptake was obtained as compared with free drugs.

Keywords: :

• breast cancer
• co-loading
• design of experiments
• imatinib mesylate
• paclitaxel
• PLGA nanoparticles
• protamine
• quality by design

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17435889.2024.2353557

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.